Breast cancer is a cancer that starts in the cells of the breast in women and men. Worldwide, breast cancer is the second most common type of cancer after lung cancer (about 10% of all cancer incidences) and the fifth most common cause of cancer death.
Due to the high impact of breast cancer an early diagnosis of breast cancer is essential, especially since this improves the survival rate of breast cancer patients. Therefore in breast cancer, regular mammography and early diagnosis is of high importance. This increases the chances that the lymph nodes are not infiltrated, that the tumor can be surgically removed and local or regional therapy (radiation therapy) is sufficient.
In many cases of early and advanced breast cancer local or regional treatment is insufficient. In those cases, establishing the second line therapy most suited for each breast cancer patient is essential. After removal of (part) of the breast, systemic treatment like chemotherapy or targeted therapy is used. With new drugs, especially those targeting kinases, selection of patients using molecular diagnostics appears to be critical for success. Biomarkers like the estrogen receptor (ER), the progesterone receptor (PR) or the human epidermal growth factor receptor 2 (HER2) play an important role in deciding whether hormone therapy, Herceptin or another drug is included in the treatment of choice.
Determining the type of breast cancer is therefore important for providing the most suited treatment of the patient. It is known that for early and advanced breast cancer both in pre- and postmenopausal women, Tamoxifen or another anti-estrogen like raloxifene, lasofoxifene or bazedoxifene, is a suited treatment for an estrogen receptor positive (ER+) and/or an progesterone receptor positive (PR+) breast tumor. Tamoxifen is an anti-estrogen from the group of SERMs (Selective Estrogen Receptor Modulator). Recently, aromatase inhibitors have become the drugs of choice for treatment of breast cancer in postmenopausal ER+ or PR+ women. Aromatase inhibitors prevent the formation of estrogens by inhibition of enzymes that catalyze the conversion of androsterons to estrogen. By blocking the action of the enzyme aromatase, no more estrogens are produced in the body.
Human epidermal growth factor receptor 2 positive (HER2+) breast cancer is currently treated with Herceptin. For breast tumors that are estrogen receptor negative, progesterone receptor negative and HER2 negative, no targeted therapy is available and in general prognosis is poor.
For determining whether a breast tumor is either ER positive or negative, HER2 positive or negative and/or PR positive or negative usually immunohistochemical, PCR or FISH methods are used. These methods localize the estrogen, human epidermal growth factor or progesterone receptors in the tumor cells using antibodies binding specifically to the estrogen, human epidermal growth factor or progesterone receptors. However, these immunohistochemical measurements are not well standardized yet and their reliability to predict hormone therapy responses is limited.
The presence of estrogen receptors is the best indicator of response to anti-estrogen agents such as tamoxifen. However, 30% to 40% of women with estrogen receptor positive breast cancer will develop distant metastases and die despite tamoxifen treatment, which percentage is even higher for ER+ PR− (60%).
Consequently, there remains need for methods that provide a fast and accurate measurement of the estrogen, human epidermal growth factor or progesterone receptor status in breast tumors. These methods would enable the identification of the type of breast cancer at an early stage, and more specifically provide an early determination of the most suited treatment of the breast cancer patient.
The present invention aims at providing methods and devices for determining the estrogen receptor status of patients suffering from breast cancer. The present invention also aims to provide methods and devices for predicting the response of patients diagnosed with breast cancer to specific medicaments. The method of the present invention therefore adds to the existing HER2, ER and PR immunohistochemical assays currently used to select therapies in breast cancer patients.